The Clinical Inadequacy of the Placebo Model and the Development of an Alternative Conceptual Framework

Abstract

Placebo effects are often attributed to clinical interactions and contextual factors that affect expectations of the patient about the treatment and result in symptom changes. The prevailing conceptualization consists of an undifferentiated placebo response that needs to be minimized in controlled investigations and maximized in clinical practice. However, treatment outcome is the cumulative result of the interaction of several classes of variables with a selected treatment: living conditions (housing, nutrition, work environment, social support), patient characteristics (age, sex, genetics, general health conditions, personality, well-being), illness features and previous therapeutic experience, self-management, and treatment setting (physician's attitude and attention, illness behavior). Such variables may be therapeutic or countertherapeutic, and are unlikely to be simply additive. In certain patients their interactive combination may lead to clinical improvement, whereas in other cases it may produce no effect, and, in a third group, it may lead to worsening of the condition. Maximizing patients' expectations does not necessarily result in sustained effects and, in due course, may actually lead to worsening of the condition (violation of expectations). In this paper, we outline a multifactorial conceptual model that may have implications for the design of clinical trials as well as for clinical practice, with special reference to psychopharmacology and psychotherapy. The effects of drug treatment may be potentiated by specific nonpharmacological treatment strategies, and this synergism may disclose significant differences against placebo. Medical outcomes may be unsatisfactory not because technical interventions are missing, but because our conceptual models and thinking are inadequate.

Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety

“…In line with recent recommendations [70], deteriorations with respect to the primary behavioral outcome were explored. Visual inspection of self-reported anxiety measures before and after EXP training suggested that 5 out of 23 subjects displayed a numerical increase in anxiety while 9 subjects displayed a numerical anxiety increase following the SHC training.…”

“…Importantly, the proportion did not differ between the EXP and the SHC training arguing against specific effects of amygdala- vlPFC connectivity training. The outcome of an intervention is influenced by multiple factors [70], including pretreatment individual differences. The identification of markers that predict treatment response [83] and the use of repeated training sessions may increase the number of participants that respond to rt-fMRI NFTs.…”

Iatrogenic Factors in Psychopathology

“…1), where all may contribute to the presentation of a clinical condition. These pathways include biological, psychological, and social factors of iatrogenic nature, whose consequences (syndromes, symptoms and any sort of problem) may be considered as potentially counter-therapeutic [72]. …”

Acceptance and Commitment Therapy for the Management of Suicidal Patients: A Randomized Controlled Trial

“…During the follow-up period, 3 participants attempted suicide in the relaxation group versus 1 patient in the ACT group. In order to address multifactorial ingredients of treatment outcome [23], description of patients having attempted suicide during the study period are available in the supplementary material.…”